Chronic Renal Failure
in Children
Maria Ferris, MD
August 2001
Chronic Renal Failure
in Children
• CRF is a stage of renal dysfunction
with GFR ~ 75 ml/min/1.73 m2 to
severe renal failure with GFR ~ 10
ml/min/1.73 m2 (ESRD)
Epidemiology
• The incidence of ESRD is about 1-3
children/million total population
• Incidence in children 0-19 years of age
adjusted for age, race and sex averages
10-12/million adjusted population
• When examined by race, Asian, Pacific
islanders and Native Americans have
lower rates, and African Americans have
higher rates of ESRD in 15-19 years of age
Epidemiology
• Current US data are thought to
underestimate the true childhood
incidence rate by about 10-13% because
of under reporting
• Over the past decade, ESRD in US
children has remained constant between
0-4 years but has increased by 50%
between the ages of 5-19 years
Estimating Progression of
Renal Disease
• The relation of log serum creatinine (1/SCr) versus
time has been used
• Creatinine clearance can overestimate GFR for two
reasons
– Tubular secretion of Cr increases in a variable
but significant manner
– GI CrCl becomes a larger percentage of total
clearance
• In patients with CRI, both Cr secretion & excretion
are affected by protein intake and HTN Rx
Diet and CRI
• Dietary protein intake is a potent modulator
of GFR
• It has been proposed that limiting protein
intake may slow progression
• Any decrease in GFR results in an  in the
transcapillary hydraulic pressure in snGFR
within the remaining nephrons
Diet and CRI
• It has been proposed that glomerular
hyperfiltration (although initially an
adaptive response to maintain GFR) is
responsible for the progression of
glomerulosclerosis &  renal function
Dietary Protein and
Renal Function
• GFR is affected by both acute and
sustained changes in protein intake
• In rats,  protein diets with partial renal
ablation accelerates glomerulosclerosis
(not in dogs or apes)
• Because of growth, studies in children
prescribe protein intake no lower than the
RDA (0.6-0.8 g/kg/day up to 40 g/day)
Dietary Protein and
Renal Function
• Adults and children with CRF maintain
nutrition status when given very low
protein diet supplemented with ketoacids
• In adults, the MDRD study was unable to
demonstrate that either low protein diets
or very low protein diets supplemented
with ketoacids were effective at slowing
the rate of progression of disease
Limiting Phosphorus Intake
• Phosphorus intake is closely linked to
protein intake
• It is not clear whether there is a direct role
of dietary phosphorus in accelerating
progression of disease
Limiting Lipid Intake
• Hyperlipidemia is associated with development of
glomerulosclerosis in animal models
• Lipid lowering strategies appear to decrease
renal injury in rats, but results are equivocal in
humans
• Mechanisms include uptake of Low Density
lipoproteins by PMN’s within the glomerulus & 
production of renal thromboxanes in  lipidemia
Limiting Lipid Intake
• Polyunsaturated fatty acids are precursors
for prostacyclin (PGI2)and thromboxanes
(TxA2):
– PGI2 : a potent vasodilator and platelet
antagonist
– TxA2: a vasoconstrictor with platelet agonist
properties
• The specific inhibition (TxA2) preserves
renal Fxn &  histologic damage in rats
Limiting Lipid Intake
•  PGI synthesis w/PO linoleic acid   
  urinary PGI excretion &  renal Fxn
• Dietary fish oil w/ -3 fatty acids slows the
rate of progression in adults with IgA GN
Limiting HTN & Proteinuria
• Proteinuria affects renal Fxn in glomerular
diseases and DM
• The mechanism of anti-HTN Rx is not
clear: may be related to the improvement
of systemic BP or the intrarenal BP
• Even when proteinuria is not a clinical
problem, BP control is effective in slowing
the progression of renal failure
Adaptation to Loss
of Renal Mass: Glomerulal
• As renal mass , the residual renal tissue
undergoes physiologic and morphologic
change that includes intraglomerular
capillary HTN, glomerular hyperfiltration &
hypertrophy.
• Although the initial effects of this
adaptation is to restore renal Fxn, it may
be ultimately causing long-term damage to
the kidney.
Adaptation to Loss
of Renal Mass: Na
• Na homeostasis is well maintained
throughout the course of CRI
• Under normal circumstances, healthy
children can adapt to Na intake of < 1 to
>500 mEq/day (25,000 mEq Na filtered/day
or 180 L/day x 140 mEq Na/L)
• More than 99% of the filtered Na is
reabsorbed, < 1% is excreted
Adaptation to Loss
of Renal Mass: Na
• Each glomerular reabsorbs less and
excretes more Na
• Although patients with CRI retain their
ability to alter Na balance w/change in Na
intake, they can’t adapt rapidly (in acute
Na load is excreted less efficiently, so ECF
volume ; in acute  in Na intake  to ECF
volume contraction)
Adaptation to Loss
of Renal Mass: Na
• In CRI, Na conservation is less efficient
• In obstructive uropathy and  GFR, Na is
not retained effectively  ECF contraction
• Na losses then contribute to poor growth
– Can be treated with Na supplementation
Adaptation to  of Renal Mass: K
• Normally, 90% of daily K intake is excreted
in urine (the balance in stool)
• K homeostasis is usually maintained until
GFR is < 10% of normal by a combination
of  colonic and distal tubular K secretion
• In CRF,  aldo excretion stimulates Na-K
exchange in the distal tubule and colon
Adaptation to  of Renal Mass: K
• Spironolactone or ACE inhibitor (Inhibite
aldo) should be used with caution  K
• Some patients with CRI have
hyperreninemia (unknown cause),
hypoaldosteronism & are vulnerable to K
Hyperkalemia
• A common cause of hyperkalemia and CRI is
dietary or the use of K-salt substitutes
• Seen in CRI with the development of ECF volume
depletion, acidosis or oliguria
• May occur due to transient pseudohypoaldo with
ACE inhibitors or with obstructive nephropathy
• Children with renal salt wasting are more prone to
hyperkalemia, particularly when salt supplements
are omitted
Hypokalemia
• Uncommon in children with CRI
• Children receiving diuretic therapy or
those with RTA sometimes develop  K
requiring K supplements
• As renal function declines, a tendency for
hypokalemia decreases and K
supplements may be discontinued
Hydrogen+/ Bicarbonate
• Maintenance of normal acid-base balance is
due to reabsorption of filtered bicarbonate
by proximal tubule and secretion of acid
equivalence by the distal tubule
• Net acid production is from bone formation
& catabolism of sulfa-containing amino a.
• Metabolic acidosis is common in patients
with CRI when GFR  to < 50 ml/min/1.73 m2
Hydrogen+/ Bicarbonate
• Net acid excretion varies in adults from 1-2
mEq/kg/day & in children 2-3 mEq/kg/day
(bone & dietary net acid input)
• With bone reabsorption, Ca and hydroxyl
ions are released; hydroxyl ions accept
hydrogen ions
• In acute acidosis, bone buffering occurs
but in chronic acidosis is less certain
Hydrogen+/ Bicarbonate
• Total ammonia synthesis  as GFR  & the
ability to excrete acid 
• In humans, the threshold for bicarbonate
reabsorption is  and  bicarbonate
wasting urine may be alkaline despite
acidosis
• Renal bicarbonate excretion is  in
hyperparathyroid states, with ECF volume
expansion and Fanconi syndrome
Alkalosis
• When ECF volume is maintained, renal bicarbonate
excretion is large and metabolic alkalosis from
alkali treatment is unusual.
• Only with very low GFR does alkali therapy exceed
this capacity and result in metabolic alkalosis
•  ECF volume (diuretics or renal salt wasting)
usually is associated with NaCl depletion.
• If alkali is given without giving chloride then
contraction metabolic alkalosis results
Water
• Most patients maintain normal water balance
until late in the course of CRI
• Concentration ability is limited if the patient
has dysplasia or medullary tissue disorder
• Total osmolar clearance is unchanged and free
water clearance  as GFR 
• As GFR  urine becomes isotonic or hypotonic
Water
• Patients with high salt & protein intake and
polyuria will  urine volume if they  salt and
protein intake
• Children with obstructive uropathy need to be
encouraged to drink water ad lib ast hey do not
concentrate their urine
Calcium
• In children with CRI, both dietary Ca uptake
and urinary Ca excretion are 
• GI Ca absorption is  as a result of 
circulating 1,25 hydroxy Vitamin D levels
•  PTH increases both bone Ca release and
renal Ca reabsorption
Calcium
• In severe renal failure, total urinary Ca
excretion remains low and FeCa 
• When Vitamin D is given to prevent renal
osteodystrophy, hypercalcemia, hypercalciuria
and decreased GFR may occur
Phosphorus
• Serum phosphorus levels are maintained WNL
until GFR decreases to about 25% of normal
• If phosphorus intake remains high, the release
of phosphate is  in patients with CRI
• The FePO4 
• It is proposed that a decrease in renal
phosphate excretion  secretion of PTH
Phosphorus
•  PTH levels cause an increase in fractional
excretion of phosphorus
• The  FePO4 does not depend on hyperpara, as
it can occur in parathyroidectomized animals
in which PTH is absent or at base-line level
Metabolic Toxins
• High Urea may be toxic
• If SUN is 100 = weakness, malaise, lethargy &
platelet dysfunction
• Even if SUN is 190 few adtl/ uremic symptoms
occur not a major metabolic toxin
• ?PTH, guanidines, methylamines, phenols &
polyamines
Metabolic Adaptation
Anemia (Causes)
•  EPO by the peritubular interstitial cells within
the inner cortex and outer medulla.
•  Fe
•  RBC Survival, bone marrow inhibition
• Intestinal and later HD-related loss
Anemia in Children
• With GFR 20-35 ml/min/1.73m2
• Hgb in pre-pubertal children is 2g/dL
lower than adults
• Rx with r-HuEPO (prior to ESRD) 
appetite but not Wt and Ht SDS. Side
effects: Fe  and HTN
Growth and Development
Malnutrition
• Anorexia is a major c/o (? Taste sensation
altered)
• When diet <80% RDA = growth retardation
• Catch up growth does not catch up to peers
• Calorie use less efficient in CRF ?
• Intakes > 100% RDA are not desirable
Nitrogen Balance
• N intake = loss (stool, urine, skin) normally
• Children have a higher protein
requirement than adults (greater lean
body mass) & need to be in (+) N
balance to support growth
Nitrogen Balance
• Uremia alone may increase protein
catabolism and/or be associated with
poor utilization of protein
• With  azotemia, PO protein should be
progressively reduced to minimal levels
in an attempt to keep the SUN <100
Nutrition
• With CRF recommended diet is CHO’s
50, fat 35-40, and protein of high
biologic value 5-10 gm/day ( protein
intake to 0.6 gm/ kg/day, or to 0.3
gm/kg/day if combined with a.a. or k.a.)
• The CHO consumption should be at the
within four hours of protein ingestion, to
prevent protein catabolism
Statural Growth Failure
• Malnutrition plays a major role in growth failure
in infants but not in older children
• In pre-ESRD pubertal children the growth spurt
is delayed and has a smaller Pk Ht velocity, so
mean Ht gain is 50% of normal
• CRI children are less affected than ESRD
Intellectual Development
Neurologic and Cognitive Function
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In first 2 years brain vol. doubles to 80% final
In CRI Performance IQ worse than verbal IQ
Test scores improve after Txp
EEG Changes w/  PTH which respond to
parathyroidectomy
• Psychosocial adjustments
Care of a Child with CRI
Setting
• Diet records q. 2-6 months
• Multidisciplinary care
• Continued education and monitoring
Care of a Child with CRI
Measurements
• Growth and GV
• Triceps skin folds thiickness and mid-arm
circumference difficult in infants
• BUN/Cr >20 =  vol/Protein, <10 malnutrition
• Labs & Bone age
• Developmental evaluations
Care of a Child with CRI
Caloric Intake
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Feeding strategies
Supplements
Feeding tube
TPN
Drugs/Medications
Therapy for Growth Failure
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Nutrion
Fluid and electrolytes
PTH
EPO
Psychological Rx
Drugs/Medications
Therapy for Growth Failure
• Growth Hormone at 0.35 mg/Kg or 30 Units/m2
Drug Use in Children with
Decreased Renal Function
• Correction of doses by GFR
• Drug interactions